A Comparative Analysis of Variations in Synthetic Biology Regulation.

Synthetic biology is an emerging technology with the potential to offer significant scientific developments to various fields such as with pharmaceutical development. Despite such promise, it has uncertain potential risks that may yield lasting and consequential damage to humans, animals, and the environment. In order to address such risks, national governments may utilize regulatory instruments to capture the process of synthetic biology development. However, where synthetic biology remains an uncertain technology with limited experimental testing, the regulation and governance of synthetic biology may vary from one government to another. This dissertation seeks to explain why such variations in the regulation of synthetic biology arise across various governments. Focusing on the specific cases of the United States, Singapore, and the European Union, these variations are hypothesized to be caused by elements of risk culture, or the political and institutional factors that influence local regulatory decision making. This hypothesis is tested via a literature analysis and an assessment of subject expert interviews from each case via qualitative discourse analysis. More specifically, findings from this dissertation indicate that of these factors, historical path dependency of the regulation of genetically modified organisms and similar biotechnologies has the strongest effect with respect to influencing variations of regulation for synthetic biology.PHDHealth Services Organization & PolicyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/135739/1/bdtrump_1.pd

INFLUENCE OF GLUTARALDEHYDE AND/OR OSMIUM TETROXIDE ON CELL VOLUME, ION CONTENT, MECHANICAL STABILITY, AND MEMBRANE PERMEABILITY OF EHRLICH ASCITES TUMOR CELLS

Effects of fixation with glutaraldehyde (GA), glutaraldehyde-osmium tetroxide (GA-OsO4), and osmium tetroxide (OsO4) on ion and ATP content, cell volume, vital dye staining, and stability to mechanical and thermal stress were studied in Ehrlich ascites tumor cells (EATC). Among variables investigated were fixation time, fixative concentration, temperature, osmolality of the fixative agent and buffer, total osmolality of the fixative solution, osmolality of the postfixation buffer, and time of postfixation treatment in buffer (Sutherland, R. M., et al. 1967. J. Cell Physiol. 69:185.). Rapid loss of potassium, exchangeable magnesium, and ATP, and increase of vital dye uptake and electrical conductivity occurred with all fixatives studied. These changes were virtually immediate with GA-OsO4 or OsO4 but slower with GA (in the latter case they were dependent on fixative temperature and concentration) (Foot, N. C. 1950. In McClung's Handbook of Microscopical Technique. 3rd edition. 564.). Total fixative osmolality had a marked effect on cell volume with OsO4 but little or no effect with GA or GA-OsO4. Osmolality of the buffer had a marked effect on cell volume with OsO4, whereas with GA or GA-OsO4 it was only significant at very hypotonic buffer osmolalities. Concentration of GA had no effect on cell volume. Osmolality of the postfixation buffer had little effect on cell volume, and duration of fixation or postfixation treatment had no effect with all fixatives. Freezing and thawing or centrifugal stress (up to 100,000 g) had little or no effect on cell volume after all fixatives studied. Mechanical stress obtained by sonication showed that OsO4 alone produced poor stabilization and that GA fixation alone produced the greatest stabilization. The results indicate that rapid membrane permeability changes of EATC follow fixative action. The results are consistent with known greater stabilizing effects of GA on model protein systems since cells were also rendered relatively stable to osmotic stress during fixation, an effect not noted with OsO4. After fixation with GA and/or OsO4 cells were stable to osmotic, thermal, or mechanical stress; this is inconsistent with several earlier reports that GA-fixed cells retain their osmotic properties

Materials by "Design": Rational Discovery of New Ternary Chalcogenides and Their Electronic Behavior

From the bronze age to the silicon age, the discovery of new materials has driven the technology of the future. Historically the discovery of new materials is an investigative process rather than a predictive one. Utilizing homologous series to guide the investigative process allows for rational designs to predict specific structures with desired properties. However, the desired products are not always achieved, and additional experiments are conducted to isolate new compounds and determine their properties. This exact process has led to the discovery of over four new compounds contained in this dissertation, as well as verified existing understanding of similar compounds. Chapter 1 contains introductory topics to understand the enclosed works and the experimental tools utilized. Chapter 2 discusses the synthesis and physical properties of the new misfit compound (BiSe)1.15(TiSe2)2, discovered using the homologous series (MX)m(1+δ)(TX2)n. Intercalation with copper, Cux(BiSe)1.15(TiSe2)2, (0 ≤ x ≤ 0.10) is also reported, but unlike CuxTiSe2, no superconductivity is observed down to T = 0.05 K, though this effective approach elucidates the impact of dimensionality on charge density wave formation and superconductivity. Chapters 3 and 4 are the result of expanding the homologous series (MX)m(1+δ)(TX2)n to include iridium, of interest due to strong spin-orbit coupling. Though no misfit compounds were observed, three Ir-Sn-Se compounds and an Ir-Pb-Se compound were observed. Chapter 3 describes the synthesis and physical properties of IrSn0.45Se1.55, a pyrite phase, Ir2Sn3Se3, a skutterudite phase, and Ir2SnSe5, which is layered, distorted β-MnO2 (pyrolusite) structure. All three compounds display varying degrees of anion-anion bonding and electronic structure calculations on Ir2Sn3Se3 suggest that it is topologically non-trivial under tensile strain, due to inversion of Ir-d and Se-p states. Chapter 4 describes the synthesis and physical properties of the distorted-Hollandite PbIr4Se8. Characterization measurements demonstrate disorder on the Pb site, due to the combination of lone-pair effects and the large size of the one-dimensional channels. Comparisons are made to known Hollandite and pseudo-Hollandite structures, which demonstrates that the anion-anion bonding in PbIr4Se8 distorts its structure, to accommodate the Ir3+ state

A decision analytic model to guide early‐stage government regulatory action: Applications for synthetic biology

Synthetic biology (SB) involves the alteration of living cells and biomolecules for specific purposes. Products developed using these approaches could have significant societal benefits, but also pose uncertain risks to human and environmental health. Policymakers currently face decisions regarding how stringently to regulate and monitor various SB applications. This is a complex task, in which policymakers must balance uncertain economic, political, social, and health‐related decision factors associated with SB use. We argue that formal decision analytical tools could serve as a method to integrate available evidence‐based information and expert judgment on the impacts associated with SB innovations, synthesize that information into quantitative indicators, and serve as the first step toward guiding governance of these emerging technologies. For this paper, we apply multi‐criteria decision analysis to a specific case of SB, a micro‐robot based on biological cells called “cyberplasm.” We use data from a Delphi study to assess cyberplasm governance options and demonstrate how such decision tools may be used for assessments of SB oversight.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142416/1/rego12142.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142416/2/rego12142_am.pd

CLEAR II: Evidence for Early Formation of the Most Compact Quiescent Galaxies at High Redshift

The origin of the correlations between mass, morphology, quenched fraction, and formation history in galaxies is difficult to define, primarily due to the uncertainties in galaxy star-formation histories. Star-formation histories are better constrained for higher redshift galaxies, observed closer to their formation and quenching epochs. Here we use "non-parametric" star-formation histories and a nested sampling method to derive constraints on the formation and quenching timescales of quiescent galaxies at $0.7<z<2.5$. We model deep HST grism spectroscopy and photometry from the CLEAR (CANDELS Lyman$-\alpha$ Emission at Reionization) survey. The galaxy formation redshifts, $z_{50}$ (defined as the point where they had formed 50\% of their stellar mass) range from $z_{50}\sim 2$ (shortly prior to the observed epoch) up to $z_{50} \simeq 5-8$. \editone{We find that early formation redshifts are correlated with high stellar-mass surface densities, $\log \Sigma_1 / (M_\odot\ \mathrm{kpc}^{-2}) >$10.25, where $\Sigma_1$ is the stellar mass within 1~pkpc (proper kpc). Quiescent galaxies with the highest stellar-mass surface density, $\log\Sigma_1 / (M_\odot\ \mathrm{kpc}^{-2}) > 10.25$, } show a \textit{minimum} formation redshift: all such objects in our sample have $z_{50} > 2.9$. Quiescent galaxies with lower surface density, $\log \Sigma_1 / (M_\odot\ \mathrm{kpc}^{-2}) = 9.5 - 10.25$, show a range of formation epochs ($z_{50} \simeq 1.5 - 8$), implying these galaxies experienced a range of formation and assembly histories. We argue that the surface density threshold$\log\Sigma_1/(M_\odot\ \mathrm{kpc}^{-2})>10.25$ uniquely identifies galaxies that formed in the first few Gyr after the Big Bang, and we discuss the implications this has for galaxy formation models.Comment: 13 pages, 7 figures, accepted for publication in ApJ. Includes an interactive online appendix (https://vince-ec.github.io/appendix/appendix

Incommensurate magnetism near quantum criticality in CeNiAsO

Two phase transitions in the tetragonal strongly correlated electron system CeNiAsO were probed by neutron scattering and zero field muon spin rotation. For $T <T_{N1}$ = 8.7(3) K, a second order phase transition yields an incommensurate spin density wave with wave vector $\textbf{k} = (0.44(4), 0, 0)$. For $T < T_{N2}$ = 7.6(3) K, we find co-planar commensurate order with a moment of $0.37(5)~\mu_B$, reduced to $30 \%$ of the saturation moment of the $|\pm\frac{1}{2}\rangle$ Kramers doublet ground state, which we establish by inelastic neutron scattering. Muon spin rotation in $\rm CeNiAs_{1-x}P_xO$ shows the commensurate order only exists for x $\le$ 0.1 so the transition at $x_c$ = 0.4(1) is from an incommensurate longitudinal spin density wave to a paramagnetic Fermi liquid